Specimen Margin Tops Frozen Margin as Prognostic Marker in Oral Cancer Surgery


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We concluded that the main specimen margin is significantly associated with local recurrence and is the strongest predictor of recurrence compared to the tumor bed frozen margins and the final operative margin.
— Marisa R. Buchakjian, MD, PhD

Intraoperative frozen margins from the tumor bed help to assess the prognosis of oral cancer, but the permanent specimen margin remains king, according to a retrospective cohort study reported at the 9th International Conference on Head and Neck Cancer.1

Results indicated that the rate of local recurrence was higher when the specimen margin was positive than when the frozen margin was positive (45% vs 36%) and lower when the specimen margin was negative than when the frozen margin was negative (13% vs 19%). Furthermore, additional resection to “clear” an involved frozen margin during surgery did not significantly reduce the recurrence risk relative to that seen when the margin was not involved.

“Main specimen margins and intraoperative tumor bed frozen margins combined together can predict outcomes,” commented first author Marisa R. Buchakjian, MD, PhD, a Resident in the Department of Otolaryngology–Head and Neck Surgery at the University of Iowa Hospitals and Clinics, Iowa City. However, “the main specimen margin carries more prognostic value between the two.”

“Clearing an intraoperative tumor bed frozen margin does not reduce the recurrence risk to that of an uninvolved margin,” she added.

Study Details

The investigators studied 406 patients who underwent resection for primary oral cavity squamous cell carcinoma of any stage between 2005 and 2014 at the institution. Those who underwent neoadjuvant chemotherapy or radiation therapy prior to surgery, whose resection did not have curative intent, or who had gross residual disease were excluded.

In all patients, surgeons attempted to resect the tumor with gross 1-cm margins and assessed the tumor bed intraoperatively with frozen sections. When frozen margins were found to be positive, they performed re-resection.

Study results reported at the meeting and simultaneously published2 showed that when assessed against the status of the permanent specimen margin, the status of the frozen margin had an overall accuracy of just 66%, a sensitivity of 55%, a specificity of 70%, and a false-negative rate of 45%.

“Intraoperative frozen margins from the tumor bed were unreliable tests of the main specimen resection margins and in fact would be expected to miss approximately 50% of positive main specimen margins,” Dr. Buchakjian commented.

Link to Local Recurrence

The rate of local recurrence was 45% when the specimen margin was positive, 36% when the frozen margin was positive, and 62% when the final operative margin (reflecting any re-resections and additional frozen margins obtained) was positive. On the other hand, it was 13%, 19%, and 22%, respectively, when these margins were negative.

Frozen Margin Accuracy and Prognostic Value in Oral Cancer

  • A retrospective cohort study of 406 patients with oral cavity cancer found that intraoperative frozen margins from the tumor bed had only a 66% accuracy for predicting the status of permanent specimen margins.
  • The rate of local recurrence was higher when the specimen margin was positive than when the frozen margin was positive (45% vs 36%) and lower when the specimen margin was negative than when the frozen margin was negative (13% vs 19%).
  • Clearing of involved frozen margins intraoperatively did not significantly reduce the rate of local recurrence relative to that seen when the frozen margin was not involved.

“From these data, we concluded that the main specimen margin is significantly associated with local recurrence and is the strongest predictor of recurrence compared to the tumor bed frozen margins and the final operative margin,” she said. Combining margin statuses provided some additional prognostic information with respect to both local recurrence and survival, but status of the specimen margin continued to have the largest influence.

Finally, the local recurrence rate was 13% for the group of patients having both an uninvolved frozen margin and an uninvolved specimen margin. This rate compared with 27% for the group with an involved frozen margin (showing either invasive or in situ disease) that was cleared by additional resection, 29% for the group with an involved frozen margin that was not cleared, and 34% for the group with an uninvolved frozen margin but an involved specimen margin.

“Additional resection to achieve a negative intraoperative tumor bed frozen margin did not alter prognosis and did not change the prognostic information derived from a positive or involved main tumor specimen margin in our study,” Dr. Buchakjian concluded. ■

Disclosure: Dr. Buchakjian reported no potential conflicts of interest.

References

1. Buchakjian MR, Tasche KK, Pagedar NA, Sperry SM: Margin assessment in oral cancer surgery. 2016 International Conference on Head and Neck Cancer. Abstract S017. Presented July 17, 2016.

2. Buchakjian MR, Tasche KK, Robinson RA, et al: Association of main specimen and tumor bed margin status with local recurrence and survival in oral cancer surgery. JAMA Otolaryngol Head Neck Surg. July 17, 2016 (early release online).


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